High-Dose Trivalent Inactivated Influenza Vaccine Improves Seroconversion Rate in RA

A high-dose trivalent vaccine may enhance antibody production against influenza in people with RA.

The following article is part of conference coverage from the 2018 American College of Rheumatology and Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in Chicago, Illinois. Rheumatology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in rheumatology. Check back for the latest news from ACR/ARHP 2018 .

CHICAGO — Administration of a high-dose trivalent inactivated influenza vaccine (HD-TIV) may result in improved vaccination responses compared with use of the standard dose quadrivalent inactivated influenza vaccine (SD-QIV) in patients with seropositive rheumatoid arthritis (RA).1 These results, presented at the 2018 ACR/ARHP Annual Meeting, held October 19-24, in Chicago, Illinois, suggest that HD-TIV may improve post-vaccine response in immunocompromised patients, including those with RA.

Researchers at McGill University conducted a randomized, double-blind, active-controlled trial in adults with rheumatoid factor- or anti-cyclic citrullinated peptide antibody-positive RA recruited from a tertiary care center (ClinicalTrials.gov identifier: NCT02936180). The recruited participants had a mean age of 61, and 80% were women.

Study participants (n=279) were randomly assigned to receive either SD-QIV (n=139, 15 μg of hemagglutinin [HA] per strain) or HD-TIV (n=140, 60 μg of HA per strain) during the 2016–2017 and 2017–2018 Northern-Hemisphere influenza seasons.

Influenza vaccine strains used in year 1 and 2 were A/HongKong/4801/2014(H3N2), B/Brisbane/60/2008. Other influenza vaccine strains included A/California/7/2009(H1N1) in year 1 and A/Michigan/45/2015(H1N1) in year 2.

Seroconversion and seroprotection rates were analyzed utilizing pre- and post-vaccine serum HA inhibition (HI) titers. Seroconversion was defined as at least a 4-fold increase in HI antibody titers from baseline. Seroprotection rate was defined as percent with HI titers ≥1:40 at day 28.

The study participants were stratified into 3 groups according to treatment received for 3 months prior to study enrollment: disease-modifying antirheumatic drugs (DMARDs; n=138), anti-cytokine therapy (n=92), anti-B-cell therapy and small molecules (n=49).  Pre-vaccine seroprotection rates were similar in the HD-TIV and SD-QIV groups.

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Vaccination response rates were higher in patients receiving HD-TIV compared with patients receiving SD-QIV (H3N2, 22.3% vs 8.6%; B/Brisbane, 44.6% vs 28.6%; H1N1, 51.1% vs 30.0%). Seroprotection rates were also increased in patients receiving HD-RIV (H3N2, 48.5% vs 30.9%; B/Brisbane, 60.9% vs 50.7%; H1N1, 80.4% vs 73.5%).

Study participants receiving HD-TIV were 2.8 times more likely to H3N2 seroconvert (odds ratio [OR], 2.84; 95% CI, 1.38–5.87), 2 times more likely to B/Brisbane seroconvert (OR, 1.91; 9% CI, 1.15-3.17), and 2.3 times more likely to H1N1 seroconvert (OR, 2.33; 95% CI, 1.42-3.85).

Vaccine dose and patient age were the only independent predictors of vaccine serologic response after logistic regression analysis.

“The McGill study shows that HD-TIV provides better seroprotection against influenza in RA patients,” stated the study’s presenting author Ines Colmegna, MD, associate professor, McGill University, in an accompanying press release.2 “These results together with the fact that the HD-TIV was as safe as the SD-TIV may lead to changes in practice (i.e. recommendation to use HD instead of SD influenza vaccine in RA) and inform public health decisions.” 

For more coverage of ACR/ARHP 2018, click here.


  1. Colmegna I, Useche M, Rodriguez K, et al. Efficacy of high-dose versus standard-dose influenza vaccine in seropositive rheumatoid arthritis patients. Presented at: ACR/ARHP 2018 Annual Meeting; October 19-24, 2018; Chicago, IL. Abstract 837.
  2. High-dose vaccine enhances production of antibodies against flu in RA patients [press release]. Chicago, IL: American College of Rheumatology. Published October 20, 2018. Accessed October 21, 2018.

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